The ototoxicity of neomycin and its concentration in the perilymph after direct application on the round window membrane were studied. After placing 5 mg of neomycin on the round window membrane of guinea pigs for various time intervals, concentration of the drug in the perilymph was determined by high performance liquid chromatography, and the cochlea was examined by light microscopy. Neomycin penetrated the round window membrane quite easily, and its concentration in the perilymph became extremely high in a short time and then decreased gradually. This indicates that high concentration of neomycin in the perilymph can be attained by application of a small amount of the drug on the round window membrane. Ototoxicity of neomycin was observed after application for 4 hours. Cochlear damage increased as neomycin application time became longer, but no consistent relationship was noted between the concentration of neomycin and the amount of damage. This result is discussed from the point of concentration and persistence of the drug in the inner ear fluids.
MittelmanH. Ototoxicity of “ototopical” antibiotics: Past, present, and future. Trans Am Acad Ophthalmol Otolaryngol1972; 76: 1432–43.
2.
PaparellaMMOdaMHiraideFBradyD. Pathology of sensorineural hearing loss in otitis media. Ann Otol Rhinol Laryngol1972; 81: 632–47.
3.
PaparellaMMGoycooleaMVMeyerhoffWL. Endolymphatic hydrops and otitis media. Laryngoscope1979; 89: 43–54.
4.
HaradaTKawabataINomuraY. Experimental study on the permeability of the round window membrane. Otol Fukuoka (Jibi To Rinsho)1982; 28 (suppl 3) :857–62.
5.
OkunoTNomuraY. Permeability of the round window membrane. Arch Otorhinolaryngol1984; 240: 103–6.
6.
SmithBMMyersMG. The penetration of gentamicin and neomycin into perilymph across the round window membrane. Otolaryngol Head Neck Surg1979; 87: 888–91.
7.
StuppHKüpperKLaglerFSousHQuanteM. Inner ear concentrations and ototoxicity of different antibiotics in local and systemic application. Audiology1973; 12: 350–63.
8.
HuyTran Ba PManuelCMeulemansASterkersOAmielC. Pharmacokinetics of gentamicin in perilymph and endolymph of the rat as determined by radioimmunoassay. J Infect Dis1981; 143: 476–86.
9.
HaradaTIwamoriMNagaiYNomuraY. Analysis of aminoglycoside antibiotics as benzoyl derivatives by high-performance liquid chromatography and its application to the quantitation of neomycin in the perilymph. J Chromatogr1985; 337: 187–93.
10.
Von IlbergCArnoldWRitterR. Ursachen und Beeinflussung der Ototoxizität des Streptomycins und verwandter Antibiotika. Laryngol Rhinol Otol (Stuttg)1974; 53: 112–20.
11.
VoldrichL. The kinetics of streptomycin, kanamycin and neomycin in the inner ear. Acta Otolaryngol (Stockh)1965; 60: 243–8.
12.
VrabecDPCodyDTRUlrichJA. A study of the relative concentrations of antibiotics in the blood, spinal fluid, and perilymph in animals. Ann Otol Rhinol Laryngol1965; 74: 688–705.
13.
WagnerWHChouJTYvon IlbergCRitterRVosteenKH. Untersuchungen zur Pharmakokinetik von Streptomycin. Arzneim Forsch1971; 21: 2006–16.
14.
JuhnSKRybakLPPradoS. Nature of blood-labyrinth barrier in experimental conditions. Ann Otol Rhinol Laryngol1981; 90: 135–41.
15.
OhtaniIMizunoSMafuneNOmataTOuchiJ. Experimental study of kanamycin concentration in blood, cerebrospinal fluid and perilymph in rabbits. Fukushima J Med Sci1976; 22: 11–8.
16.
RussellNJFoxKEBrummettRE. Ototoxic effects of the interaction between kanamycin and ethacrynic acid. Acta Otolaryngol (Stockh)1979; 88: 369–81.
17.
ToyodaYTachibanaM. Tissue levels of kanamycin in correlation with oto- and nephrotoxicity. Acta Otolaryngol (Stockh)1978; 86: 9–14.
18.
WatanabeYNakajimaROdaRUnoMNaitoT. Experimental study on the transfer of kanamycin to the inner ear fluids. Med J Osaka Univ1971; 21: 257–63.
19.
BrummettREFoxKEBrownRTHimesDL. Comparative ototoxic liability of netilmicin and gentamicin. Arch Otolaryngol1978; 104: 579–84.
20.
FederspilPSchätzleWTieslerE. Pharmacokinetics and ototoxicity of gentamicin, tobramycin, and amikacin. J Infect Dis1976; 134 (Suppl) :S200–5.
21.
HarpurESGondaI. Analysis of the pharmacokinetics of ribostamycin in serum and perilymph of guinea pigs after single and multiple doses. Br J Audiol1982; 16: 95–9.
22.
OhtaniIOhtsukiKAikawaTOmataTOuchiJSaitoT. Ototoxicity of aminoglycoside antibiotics by rapid intravenous injection. ORL J Otorhinolaryngol Relat Spec1982; 44: 156–69.
23.
BreuningerHGiebelWHaugH-P. Über das Eindringen von tympanal appliziertem Tetracyclin in das Innenohr des Meerschweinchens. Arch Otorhinolaryngol1977; 216: 523–4.
24.
BradyDRPearceJPJuhnSK. Permeability of round window membrane to 22Na or RISA. Arch Otorhinolaryngol1976; 214: 183–4.
25.
SteckerRHCodyDTR. Iontophoresis of 22Na and 131I into the inner ear. Arch Otolaryngol1966; 83: 213–7.
26.
SaijoSKimuraRS. Distribution of HRP in the inner ear after injection into the middle ear cavity. Acta Otolaryngol (Stockh)1984; 97: 593–610.
27.
TanakaKMotomuraS. Permeability of the labyrinthine windows in guinea pigs. Arch Otorhinolaryngol1981; 233: 67–75.
28.
GoldbergBGoycooleaMVSchlievertPM. Passage of albumin from the middle ear to the inner ear in otitis media in the chinchilla. Am J Otolaryngol1981; 2: 210–4.
29.
GoycooleaMVPaparellaMMGoldbergBCarpenterA-M. Permeability of the round window membrane in otitis media. Arch Otolaryngol1980; 106: 430–3.
30.
GoycooleaMVPaparellaMMGoldbergBSchlievertPMCarpenterA-M. Permeability of the middle ear to staphylococcal pyrogenic exotoxin in otitis media. Int J Pediatr Otorhinolaryngol1980; 1: 301–8.
31.
SchachernPAPaparellaMMGoycooleaMVGoldbergBSchlievertP. The round window membrane following application of staphylococcal exotoxin: An electron microscopic study. Laryngoscope1981; 91: 2007–16.
32.
HöftJ. Die Permeabilität und die Beeinflussung der Permeabilität der Membran des runden Fensters durch Pantocain (Tetracain). Arch Klin Exp Ohren Nasen Kehlkopfheilkd1969; 193: 128–37.
33.
BrummettREHarrisRFLindgrenJA. Detection of ototoxicity from drugs applied topically to the middle ear space. Laryngoscope1976; 86: 1177–87.
34.
GinsbergIARudnickMDHuberPS. Aminoglycoside ototoxicity following middle ear injection. III. Comparative quantitative analysis. Ann Otol Rhinol Laryngol1980; 89 (suppl 77) :17–24.
35.
KohonenATarkkanenJ. Cochlear damage from ototoxic antibiotics by intratympanic application. Acta Otolaryngol (Stockh)1969; 68: 90–7.
36.
NakaiYYamamotoKIgarashiM. Ototoxicity of topically applied antibiotics in guinea pigs and squirrel monkeys. Audiology Japan1974; 17: 190–7.
HuyTran Ba PMeulemansAWassefMManuelCSterkersOAmielC. Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion. Antimicrob Agents Chemother1983; 23: 344–6.
40.
NuttallALMarquesDMLawrenceM. Effects of perilymphatic perfusion with neomycin on the cochlear microphonic potential in the guinea pig. Acta Otolaryngol (Stockh)1977; 83: 393–400.
